High-Dose Ambroxol in GBA1-Related Parkinson

Last updated: February 7, 2024
Sponsor: Agyany Pharma LTD
Overall Status: Active - Recruiting

Phase

1/2

Condition

N/A

Treatment

Ambroxol Hydrochloride

Clinical Study ID

NCT06193421
AGPI
  • Ages 30-70
  • All Genders

Study Summary

Parkinson's disease (PD), affecting 10 million people globally, lacks a cure, and current therapies only manage symptoms. A link between Gaucher disease (GD) and PD, particularly in carriers of glucocerebrosidase (GBA1) mutations, has sparked interest in developing new drugs. Despite pharmaceutical companies focusing on formulations, progress is slow. Agyany, with decades of experience in GD research, plans clinical trials using existing generic drugs for GBA-related PD and idiopathic PD. Their approach targets the misfolded enzyme glucocerebrosidase with pharmacological chaperons, inspired by success in GD using ambroxol. The strategy aims to provide a quicker path to novel therapeutic options for PD.

Eligibility Criteria

Inclusion

Inclusion Criteria: For inclusion into the trial, subjects are required to fulfill all of the followingcriteria: Newly diagnosed PD patients:

  1. Individuals who exclusively carry at least one single GBA1 variant without anyadditional genetic variants.
  2. Confirmed diagnosis of PD, by a movement disorder specialist, according to MDS PDcriteria, within a maximum of three years from the date of diagnosis, coupled with thefollowing conditions: iii. Hoehn and Yahr staged between I-II, inclusive. iv. No motor fluctuations or L-dopa induced dyskinesia.
  3. Stable anti-PD medications for ≥ 4 weeks: Subjects can take PD medications including NMDA glutamate antagonists, monoamineoxidase B (MAO-B) inhibitors, dopamine agonists, and L-Dopa.
  4. Male or female, age 30-70 years; however, if female:
  • must be using contraception measures if of childbearing potential.
  • must not be lactating.
  1. Complying with study protocol.

Exclusion

Exclusion Criteria: Eligible subjects may not have any of the following exclusion criteria:

  1. Presence of any medical, emotional, behavioral, or psychological condition that in thejudgment of the Investigator would interfere with the subject's compliance with therequirements of the study (such as clinical depression).
  2. Any other disorder that may interfere with the results of the efficacy endpoints.
  3. Currently taking another investigational drug for any condition.
  4. Use of dopaminergic treatment under these conditions:
  • L-Dopa equivalent daily dose > 400mg
  • L-Dopa daily dose > 300mg
  • L-Dopa equivalent and L-Dopa daily dose has been changed in the past 4 weeksprior to screening visit.
  1. Medical history of psychosis.
  2. Exposure to ambroxol in the last 24 months prior to screening and/or history ofadverse events to ambroxol.
  3. Exposure to dopamine receptor blocking agents, lithium, cinnarizine, amiodarone orvalproic acid in the last 12 months prior to screening.
  4. Pregnancy or lactation; female subjects of a childbearing age who are unwilling to usecontraceptive measures.

Study Design

Total Participants: 40
Treatment Group(s): 1
Primary Treatment: Ambroxol Hydrochloride
Phase: 1/2
Study Start date:
October 24, 2023
Estimated Completion Date:
April 30, 2025

Study Description

Parkinson disease (PD) is the second most common neurodegenerative disease affecting around 10 million people worldwide. It is a debilitating disorder that despite many years and billions of dollars research - there is still no cure and none of the therapeutic options truly reverse its manifestations. The realization that the relationship between Gaucher disease (GD) - the rare lysosomal storage disease - and PD, also exists in carriers of the disease (with a mono-allele mutation in glucocerebrosidase (GBA1)) has led to several attempts to develop new drugs not just for GBA-related PD, but also for PD at large. However, heretofore all pharmaceutical companies have focused on finding new formulations, mostly based on what Agyany believe is not targeting the underlying pathology, but in any case, will require several years before new drugs will reach the market. With the background of three decades working at the world's largest center for GD at Shaare Zedek Medical Center in Jerusalem, and with a different understanding of the pathological processes leading to PD among a significant number of GD patients and carriers, Agyany plans to begin clinical trials in newly diagnosed PD patients using existing generic drugs that would enable a short path for introducing novel therapeutic approach to GBA-related PD and potentially also for so called idiopathic PD (when no genetic cause is known).

Based on our understanding of the underlying mechanism of GBA1-related PD, on research done in animal models and on our own anecdotal experience, Agyany believe that pharmacological chaperons are the most reasonable therapeutic modality to achieve success. Since the misfolding of the mutant enzyme, glucocerebrosidase, is the same both in GBA1-related PD and GD, and that the ambroxol impact is the same as well, Agyany can extrapolate from the success of ambroxol to achieve reversibility of neuronopathic features (that heretofore were considered irreversible, and the best expectation was lack of deterioration), in neuronopathic GD (nGD), to potential success in GBA-related PD.

The plan is to first use generic formulations with a confirmed safety profile and repurpose their indication to PD.

Connect with a study center

  • Shaare Zedek Medical Center

    Jerusalem, 9103102
    Israel

    Active - Recruiting

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